A novel "structural difference-based selective etching" strategy has been developed to fabricate hollow/rattle-type mesoporous nanostructures, which was achieved by making use of the structural differences, rather than traditional compositional differences, between the core and the shell of a silica core/mesoporous silica shell structure to create hollow interiors. Highly dispersed hollow mesoporous silica spheres with controllable particle/pore sizes could be synthesized by this method, which show high loading capacity (1222 mg/g) for anticancer drug (doxorubicin). Hemolyticity and cytotoxicity assays of hollow mesoporous silica spheres were conducted, and the synthesized hollow mesoporous silica spheres with large pores show ultrafast immobilization of protein-based biomolecules (hemoglobin). On the basis of this strategy, different kinds of heterogeneous rattle-type nanostructures with inorganic nanocrystals, such as Au, Fe(2)O(3), and Fe(3)O(4) nanoparticles, as the core and mesoporous silica as the shell were also prepared. This strategy could be extended as a general approach to synthesize various hollow/rattle-type nanostructures by creating adequate structural differences between cores and shells in core/shell structures in nanoscale. less...

Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g-PLA and diblock copolymer PEG-PLA with functional moiety was developed in this study. The mixed micelles had well defined core shell structure which was evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA exhibited pH stimulate to enable intracellular drug delivery and outer shell of PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate for cancer specific targeting were synthesized at the end of the polymer chain. The graft and diblock copolymer self assembled to nanospheres against water with an average diameter below 120 nm without doxorubicin, and an average diameter of around 200 nm when loaded with drug. From drug released study, a change in pH destroy the inner core to lead a significant doxorubicin(Dox) release from mixed micelles. Cellular uptake of folate-micelles was found to be higher than that of non-folate-micelles due to the folate-binding effect on the cell membrane, thereby providing a similar cytotoxic effect to drug only against the HeLa cell line. In vivo study revealed that specific targeting of folate-micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate-PEG-PLA have great potential in cancer chemotherapy and diagnosis. less...

Chemomicin (CHM), an angucyclinone antibiotic extracted from the fermentation broth of Nocardia Mediterranei subsp. Kanglensis 1747-64, shows immunosuppressive activity. However, whether it can inhibit growth of tumor cells remains elusive. In the present study, we show that CHM potently inhibited the proliferations of eight various types of human tumor cell lines and non-cross resistant to multidrug-resistant cells. In contrast to action of doxorubicin, the generation of reactive oxygen species was observed as early as 30 min after addition of CHM and its process did not involve iron. The apoptotic cells with chromatin condensation and Annexin V staining markedly increased after the human hepatoma HepG2 was exposed to 1, or 2 microg/ml CHM for 24 h. In the CHM-induced apoptosis, robust increment of p53 expression, activation of caspase-3, -7, -8, -9, cleavage of PARP and the phosphorylation of p38 and JNK, were detected by Western blot analysis. Further investigation revealed the disruption of mitochondrial membrane potential in the cells with CHM incubation for 4 h. Taken together, the results demonstrated that potent proliferation inhibitory effect of CHM on tumor cells is due to activation of the apoptotic pathway. less...

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm occurring less frequently in men and even more rarely in the axilla. A 59-year-old man with severe Parkinson's disease presented with axillary EMPD. The neurological comorbidity made treatment of the EMPD problematical and prompted us to propose locoregional intra-arterial chemotherapy in single short sessions. Two innovative chemotherapeutic macrocomplexes were used: doxorubicin incorporated in large liposomes and the taxane paclitaxel incorporated in albumin nanoparticles. A therapeutic response was seen right from the first treatment and was macroscopically close to complete after four cycles. Five months after the end of treatment the patient had minimal visible disease and had enjoyed a distinct improvement in quality of life, with no noteworthy complications related to the intra-arterial chemotherapy with percutaneous transfemoral catheterization. less...

Physically diverse carbon nanostructures are increasingly being studied for potential applications in cancer chemotherapy. However, limited knowledge exists on the effect of their shape in tuning the biological outcomes when used as nanovectors for drug delivery. In this study, we evaluated the effect of doxorubicin-conjugated single walled carbon nanotubes (CNT-Dox) and doxorubicin-conjugated spherical polyhydroxylated fullerenes or fullerenols (Ful-Dox) on angiogenesis. We report that CNTs exert a pro-angiogenic effect in vitro and in vivo. In contrast, the fullerenols or doxorubicin-conjugated fullerenols exerted a dramatically opposite antiangiogenic activity in zebrafish and murine tumor angiogenesis models. Dissecting the angiogenic phenotype into discrete cellular steps revealed that fullerenols inhibited endothelial cell proliferation, while CNTs attenuated the cytotoxic effect of doxorubicin on the endothelial cells. Interestingly, CNT promoted endothelial tubulogenesis, a late step during angiogenesis. Further, mechanistic studies revealed that CNTs, but not fullerenols, induced integrin clustering and activated focal adhesion kinase and downstream phosphoinositide-3-kinase (PI3K) signaling in endothelial cells, which can explain the distinct angiogenic outcomes. The results of the study highlight the function of physical parameters of nanoparticles in determining their activity in biological settings. less...

The rare occurrence of T-cell lymphoblastic lymphoma as a primary tumor in the cavernous sinus is described. The patient, a 17-year-old girl, presented with right-sided ophthalmic and maxillary neuropathy and diplopia due to neuropathies of cranial nerves III and VI. An enhancing mass in the cavernous sinus was identified on MR imaging. Dexamethasone was prescribed but did not provide symptomatic relief. Rapid progression of symptoms led to open biopsy, and a diagnosis of T-cell lymphoblastic lymphoma was made. The patient promptly underwent aggressive chemotherapy in which a modified hyper-cyclophosphamide, vincristine, and dexamethasone without doxorubicin regimen with concurrent radiotherapy was used. The patient achieved complete remission and is currently completing the 2-year maintenance phase of chemotherapy. less...

Objective-To determine the effects of the antioxidant astaxanthin on growth of canine osteosarcoma cells with and without concurrent chemotherapeutic or irradiation insult. Sample Population-Cells from 3 established canine osteosarcoma cell lines (D17, OS 2.4, and HMPOS). Procedures-Growth-curve kinetics and cell cytotoxic effects were assessed by means of various treatment combinations and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was performed to examine previously identified signaling pathways that astaxanthin reportedly affects. Additionally, cell-cycle kinetic evaluations, soft agar colony-forming assays, and antioxidant assays were performed to better understand the effect of astaxanthin on cell growth and function. Results-Exposure to astaxanthin alone resulted in a mild to pronounced attenuation of cell proliferation in vitro, depending on the cell line, and did not interfere with the cell-death response to doxorubicin, irradiation, or peroxide-mediated insult. In some instances, astaxanthin acted in an additive fashion to augment cell death. Astaxanthin exposure increased the antioxidant potential of cells, whereas peroxide-mediated cell stress increased the antioxidant potential to the same degree as astaxanthin exposure or greater. No dramatic changes in phosphorylation of protein kinase B or upregulation of connexin 43 were detected. Conclusions and Clinical Relevance-Findings suggested that astaxanthin administration may be beneficial in treatment of dogs for osteosarcoma. Its actions as an antioxidant did not improve osteosarcoma cell survival during chemotherapeutic or irradiation insults, warranting further research into this natural compound as an adjuvant, antiproliferative treatment for osteosarcoma in dogs. less...

OBJECTIVES: Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent METHODS: To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m(2)) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. RESULTS: In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being >grade 2 in severity. CONCLUSION: Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions less...

Purpose/Objectives: To examine the influence of the proposed symptom cluster of fatigue, nausea and vomiting, and sleep disturbances on clinical outcomes defined as behavior changes, depression, and performance status in children and adolescents before and after receiving cisplatin, doxorubicin, or ifosfamide chemotherapy.Design: A prospective, descriptive, within-group, before-and-after-chemotherapy design was used.Setting: Two major childhood cancer treatment hospitals in the United States.Sample: 67 patients aged 7-18 years who were receiving chemotherapy courses of cisplatin, doxorubicin, or ifosfamide.Methods: Fatigue, depression, behavior, and performance assessments were completed on the first day of cisplatin, doxorubicin, or ifosfamide therapy and one week later. Patients wore a wrist actigraph on the nondominant hand during the course of therapy and for 48 hours after discharge from the hospital. Nausea and vomiting were measured every 24 hours during the course of therapy and for 48 hours after discharge. A linear mixed model was used to evaluate the influence of the symptom cluster. Regression analysis was used to examine the associations between performance status and the symptom cluster. Principal component analysis with varimax rotation was used to produce the correlation of sleep symptoms.Main Research Variables: Fatigue, nausea and vomiting, sleep disturbances, behavior, depression, and performance.Findings: Adolescents with the cluster of increased fatigue and sleep disturbances experienced more depressive symptoms and behavior changes. Children with higher levels of fatigue had increased depressive symptoms. The more fatigue parents perceived in their children or adolescents, the more behavior and emotional difficulties were reported.Conclusions: Fatigue, sleep disturbance, and nausea and vomiting, when clustered, impacted depressive symptoms and behavior changes in adolescents after chemotherapy. In children, fatigue alone impacted depressive symptoms and behavior changes.Implications for Nursing: Symptom clusters can have a significant impact on children's and adolescents' quality of life during cancer treatment. Early recognition and intervention for these symptoms are an important nursing role. less...

Gefitinib is an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor. The present study was aimed at evaluating the antitumor activity of gefitinib alone or in combination with other antitumor agents. Gefitinib showed higher cytotoxicity against five human tumor cell lines (HSC-2, HSC-3, HSC-4, T98G and U87MG) than against three human normal oral cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Gefitinib showed little or no growth stimulation effects at lower concentrations (so-called hormetic effect). Non-cytotoxic concentration of gefitinib effectively enhanced the cytotoxicity of docetaxel against HSC-2 and T98G cell, but failed to enhance the cytotoxicity of other antitumor agents (mitoxantrone, doxorubicin, methotrexate, cisplatin, sodium ascorbate, sodium fluoride) or herbal extracts (Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc). Gefitinib alone and combined with docetaxel induced internucleosomal DNA fragmentation and caspase-3 activation in human promyelocytic leukemia HL-60 cells, but not in HSC-2 or T98G cells. Combination treatment with gefitinib and docetaxel induced the formation of acidic organelles (stained with acridine orange) and mitochondrial shrinkage, vacuolization and production of autophagosome and the loss of cell surface microvilli, without destruction of cell surface and nuclear membranes in HSC-2 and T98G cells (demonstrated by transmission electron microscopy), suggesting the induction of autophagy in HSC-2 and T98G cells. less...